This section is intended to provide a background or context to the invention that is recited in the claims. The description herein may include concepts that could be pursued, but are not necessarily ones that have been previously conceived or pursued. Therefore, unless otherwise indicated herein, what is described in this section is not prior art to the description and claims in this application and is not admitted to be prior art by inclusion in this section.
U.S. Pat. No. 5,422,720 and U.S. Pat. No. 5,770,394 illustrate extant technology for the detection of metabolic products, particularly CO2, resulting from the growth of microorganisms present in blood culture bottles. See also U.S. Pat. No. 6,379,920 (direct comparison of the spectral features of organisms grown in standard media and in blood culture bottles) and U.S. Pat. No. 5,427,920 (detecting the presence of microbial growth through measuring the intensity of back-scattered light).
Thus, the literature describes a variety of methods for determining the presence of microorganisms in blood. The presence of microorganisms typically is detected by means of an internal indicator for the production of a microbial metabolic product, such as CO2. Illustrative in this regard are optical monitoring of changes in a CO2-sensitive disk in the bottom of blood culture bottles (U.S. Pat. No. 5,770,394) and pressure-sensitive techniques that measure increased production of CO2 in the head space of a culture bottle. Other methodology has related changes in back-scattered light peak intensity at a few wavelengths to the presence of microorganisms. For example, see U.S. Pat. No. 5,427,920.
These approaches have not been employed commercially, however, because of difficulties in the variable nature of blood compositions and changing initial conditions for a given experiment. More specifically, all of the existing microorganism detection methods have sensitivities that depend on the particular measurement technique employed and on the following factors:                1. the rate of production of metabolic CO2 or other metabolic products;        2. the transport of the metabolic products to an indicator dye (typically, dyes are immobilized in a solid matrix that is integrated with the culture bottle, for ease of detection);        3. the transport of metabolic gases from the liquid culture media to the bottle headspace; and        4. the time constant associated with reaction of metabolic products and the indicator dye.        
The constituency of a given spectrophotometric-indicator dye system determines its sensitivity to the presence of metabolic products, particularly in terms of the minimum detectable CO2 concentration. The time to detection (TTD) depends on the sensitivity of the measurement technique, the time required to reach the minimum detectable CO2 concentration, and on the transport and reaction time constants. The rate of growth and, therefore, the rate of production of metabolic CO2 depends on the initial concentration of organisms (CFU/mL of blood) and on the incubation conditions (growth media, temperature, etc.), as well as the strain of organism itself. Existing detection systems require between 108-109 microorganisms/mL for positive detection with an incubation or amplification time corresponding to the specific growth rate of each organism.
A conventional spectrophotometric-indicator dye system requires adding indicator dyes or other labels to the system, and does not yield any clinical information beyond the presence or absence of microorganisms. A system is needed, therefore, that provides for sensitive and efficient measurements of microorganisms without a requirement for additional materials and steps and provide more meaningful information about the character of the microorganisms present.